A Novel Microfluidic System for 3D Epidermis and Full‐Thickness Skin Growth for Nanoparticle Safety Assessment

Chronic skin exposure to nanoparticles (NPs) from air pollution, cosmetics, tattoo inks, and smart textiles is linked to adverse effects such as accelerated aging, dermatitis, eczema, and increased melanoma risk. However, the limited predictive power and physiological relevance of conventional in vitro models, combined with the absence of standardized protocols for assessing NP toxicity, remain a major challenge. To address these limitations, the development of skin-on-chip (SoC) systems provides a more physiologically relevant solution, surpassing the constraints of static skin cultures. Here, a novel SoC model with dynamic perfusion and a modular architecture suitable for epidermis-only (EoC) and full-thickness (FT) skin models isdeveloped. Under dynamic conditions, both models are metabolically active, exhibit enhanced barrier function, and display a morphology resembling native human skin. Exposure to titanium dioxide (TiO₂) NPs led to a 32.4% decrease in barrier integrity, a 12.1% reduction in metabolic activity, a 2.9% increase in permeability, and histological evidence of tissue damage. These alterations are associated with an early moderate inflammatory response, as indicated by the upregulation of chemokines. Collectively, these findings demonstrate that the microfluidic device functions as a versatile toxicological tool, with the biological complexity of the FT SoC enhancing its sensitivity for nanotoxicology studies.